The majority of myocardial infarction and stroke events occur in those over the age of 65. We have demonstrated during the previous grant period that measures of subclinical cardiovascular disease (CVD) and markers of inflammation and blood clotting are powerful risk factors for clinical CVD, myocardial infarction (MI) and CHD death in individuals aged 65+. We believe that measurements of these factors in proximity to the event, together with measures of subclinical disease, will significantly improve the identification of those older individuals most likely to have a clinical CVD event. We have three specific aims: 1) to measure markers of inflammation, such as fibrinogen, C-reactive protein, and ICAM-1 in sequential samples from the Cardiovascular Health Study, representing years 2, 5, 6, 7, 9, 10 of the study; 2) to measure in the same way selected cytokines and cytokine-related factors, such as IL-6, IL-1b and soluble IL-2 receptor; and 3) to measure in the same way markers of hemostatic and fibrinolytic activation, such as factor V/Va. Plasmin-a2 Anti-plasmin Complex, and D-dimer. We will evaluate each of the chosen markers as a risk factor for three outcomes: incident coronary heart disease (CHD) including fatal and non-fatal non-hemorrhagic stroke; and incident cancer of the breast, lung, colon and prostate. With these data we will test two major hypotheses: 1) prediction of events is stronger when measurements are done closer in time (< 1 year) to the clinical even compared to more distant in time (> 1 year); and 2) changes in the levels of markers over time (e.g., between baseline and the most proximate measure, or between the two most proximate measures) will be better predictors of events than a single measurement. We believe that markers will be more closely associated with MI and CHD death than with other manifestations of atherosclerotic disease such as stroke. Since there is growing evidence that inflammatory markers are related to risk of cancer, the cancer comparison group will provide information as to the specificity of these markers for CHD. It is likely our results will have important implications for prevention, diagnosis, and future therapeutic interventions in cardiovascular disease in the elderly.